The field of the invention is a catheter which is insertable into or through a subject""s urethra, or into or through another pre-existing or artificial bodily lumen of an animal, for a diagnostic or therapeutic purpose.
The use of catheters, including multi-lumen catheters, is known for many therapeutic and diagnostic medical purposes. For example, the use of urethral catheters, including multi-lumen urethral catheters, is known in the art of urology. Such urethral catheters are useful for delivering compositions, including radioactive compositions, to the urethra of a subject (e.g. Harada et al., 1993, Rad. Oncol. 11:139-145; Skarlatos et al., 1994, Urol. Int. 53:209-213). However, the use of prior art urethral catheters is limited by the ability of the practitioner to accurately identify the position of a tissue in need of radiation treatment with respect to the position of the catheter and the ability of the practitioner to accurately position a radiation source within a urethral catheter to deliver radiation to the tissue. Furthermore, prior art urethral catheters do not permit use of a first catheter to determine the position of a tissue of the subject, removal of the first catheter, and use of a second catheter to accurately provide a composition to the position of the tissue without determining the position of the tissue a second time.
Various apparatus and techniques are known in the art of brachytherapy for exposing an animal tissue to a radioactive material using a conduit placed in a cavity of the animal. By way of example, bronchial, esophageal, rectal, vaginal, and arterial conduits have been described (e.g. Raju et al., 1993, Int. J. Radiation Oncology Biol. Phys. 27:677-680).
A serious limitation of prior art intracavitary brachytherapy methods has been the inability of such methods to enable accurate and reproducible placement of radiation sources in close proximity to a tissue in need of such treatment. Significant shortcomings of prior art intracavitary brachytherapy catheters include the tendency of the catheter to move within the bodily lumen and the inability of practitioners to accurately determine both the location of a relevant tissue relative to the catheter and the location of a radiation source or pharmaceutical composition within or along the catheter. Typical prior art methods have involved attempting to identify the position of a relevant tissue, thereafter attempting to position a catheter near the relevant tissue, and thereafter attempting to position a radiation source or pharmaceutical composition within or along the catheter near the relevant tissue.
A limitation on the use of radiation and other potentially cytotoxic medical treatments is the lack of cytotoxic specificity. Radiation or drug delivered near a relevant tissue may induce death of cells in both the relevant tissue and other tissues which are located in close proximity to the relevant tissue. Because of the inaccuracy of prior art intracavitary brachytherapy methods for directing treatment only to relevant tissue, as described above, prior art methods have required the use of excess amounts of cytotoxic agents so that death of relevant tissue cells will be effected even if the agent is not accurately placed. Use of excess cytotoxic agent, however, induces damage in non-relevant tissue. Collateral damage to non-relevant tissues could be avoided if the cytotoxic agents could be delivered more accurately to relevant tissues. Accordingly, there is a great need for devices, kits, and methods for accurately delivering cytotoxic agents to relevant tissues while minimizing delivery of the agents to surrounding tissues.
The prostate is a solid organ which surrounds the urethra of the male human between the base of the bladder and the urogenital diaphragm. Benign prostatic hypertrophy (BPH) is a common condition among male humans aged 45 or older. Prostate cancer is a leading cause of death among males, and can frequently be diagnosed with the aid of a simple blood antigen-detecting test. Radiation therapy and prostatectomy are the primary treatments available for prostate cancer and prostatectomy is currently the primary treatment for BPH. Prostatectomy has numerous drawbacks, which have been widely described in the art. External beam irradiation of the prostate for the treatment of localized prostate cancer is associated with small bowel injury, radiation proctitis, and urethral stricture (Gibbons et al., 1979, J. Urol. 121:310-312). At least two groups have employed transurethral radiation therapy as a supplement to external beam irradiation of localized prostate cancer tissue (Harada et al., 1993, Rad. Oncol. 11:139-145; Skarlatos et al., 1994, Urol. Int. 53:209-213). In addition, another group has employed transurethral radiation therapy as a sole treatment for recalcitrant BPH-related urine retention (Koukourakis et al., 1994, Med. Dosimetry 19:67-72). Each of these groups employed ultrasonography, computerized tomography, or fluoroscopy imaging methods to identify the tissue to be treated or to confirm the position of the radiation source relative to the tissue to be treated. Identification of the location of tissue in need of treatment and placement of a radiation source using one of these imaging methods is dependent upon the deformability of the tissues being imaged, the body posture of the subject during the identification or placement, the position of the imaging device, and other factors which may not be easily replicated.
Failure to precisely control the amount and location of transurethrally-delivered radiation can result in damage to the urethra itself or to other organs located in close proximity thereto, including the bladder and the prostate. It is thus critical to identify the position of a tissue in need of treatment and the location of radiation source as accurately as possible.
Urethral stricture is a common complication of urological procedures, particularly following urethral intervention by a urologist (Baskin et al., 1993, J. Urology 150:642-647; Stormont et al., 1993, J. Urology 150:1725-1728). Formation of a urethral stricture is thought to involve disruption of the urothelium, followed by hypertrophy of urothelial or other tissues, resulting in stenosis. A urethral stricture may also be formed by hypertrophy of a tissue located in close proximity to the urothelium, such as prostate tissue or corpus spongiosum penis tissue in male humans or muscle tissue or spongiose erectile tissue in female humans. Non-limiting examples of urological interventions known to be associated with urethral stricture include transurethral resection of the prostate, radical prostatectomy, external beam irradiation of prostate tissue, and other urological interventions which disturb the urethra. Non-limiting examples of diseases or disorders known to be associated with urethral stricture include BPH, prostate cancer, and urethral cancer. Further details of tissues which comprise the urethra or which are located in close proximity thereto in the human are found in, for example, Williams et al., eds. (1980, Gray""s Anatomy, 36th ed., W.B. Saunders Co., Philadelphia, pp. 1408-1409).
Known treatments for urethral strictures include surgical modification of the urethra, laser-assisted modification of the urethra, urethroplasty, and urethral stent implantation (Bosnjakovic et al., 1994, Cardiovasc. Intervent. Radiol. 17:280-284; Badlani et al., 1995, Urology 45:846-856; Mundy, 1989, Brit. J. Urology 64:626-628; Quartey, 1993, Ann. Urol. 27:228-232).
Ureteric stricture is another known complication of urological procedures and of disease and disorder states. Ureteric strictures may involve hyperplasia or hypertrophy of any of the tissue layers of a ureter, namely the fibrous layer, the muscular layer, or the mucous layer, or may involve hyperplasia or hypertrophy of a tissue or organ located in close proximity to a ureter. Further details of tissues which comprise a ureter or which are located in close proximity thereto in the human are found in, for example, Williams et al., eds. (1980, Gray""s Anatomy, 36th ed., W.B. Saunders Co., Philadelphia, pp. 1402-1404). Surgical treatments are known for treatment of ureteric stricture.
A significant unmet need remains for a device and method which can be used within the urinary tract to identify the position of a tissue in need of treatment in a subject in a manner which is not dependent upon the deformability of the surrounding tissues, the position of the subject, the position of the imaging device, or other factors which are not easily replicated. As used herein, the xe2x80x9curinary tractxe2x80x9d includes the urethra, the bladder, the ureters, and the kidneys of a subject, and tissues located in close proximity thereto.
There also remains a significant unmet need for an efficacious method for treating urethral or ureteric stricture which does not exhibit the side effects and shortcomings associated with prior art methods of treating these strictures.
Numerous other catheters are known in the art for placement within a naturally-occurring bodily lumen or an artificial (i.e. surgically or traumatically formed) bodily lumen. Many of the known catheters share a common disadvantage, namely that the catheter cannot practically be secured within the bodily lumen in such a way that a point on or within the catheter may be reproducibly situated at the same location within the bodily lumen upon removal and re-emplacement of the catheter. Such reproducibility is critical if the same catheter is to repeatedly used to deliver agents (e.g. radionuclides) for which the tolerance for misplacement is low. This reproducibility is also critical if matched pairs or sets of catheters are to be used cooperatively.
The catheters, kits, and methods of using them described herein overcome these shortcomings.
The invention relates to a graduated catheter for reproducibly seating within a bodily lumen of an animal. The catheter comprises
(a) a tubular body having a distal portion,
(b) an expandable member on the distal portion of the tubular body, and
(c) an indicator associated with the tubular body for indicating a reference position within the bodily lumen. In one embodiment, the tubular body has a proximal portion and a lumen extending longitudinally therein from the proximal portion. The expandable member may, for example, be a balloon wherein at least one lumen extends from the proximal portion of the tubular body to the interior of the balloon. The balloon may, for example, be disposed about the distal portion of the catheter tube.
The graduated catheter of the invention may further comprise a movable element having an indicator associated therewith. The position of the movable element with respect to the tubular body may be determined by comparing the position of the indicator associated with the movable element with the position associated with the indicator of the graduated catheter. The graduated catheter may also comprise a plurality of the indicators longitudinally spaced along the catheter tube.
In an important embodiment, the graduated catheter of the invention, the catheter tube includes a second lumen extending longitudinally into the catheter tube from the proximal portion. The catheter may further comprising a radiation source, a radiation source positioner, or both disposed within the second lumen. The radiation source may, for example be a radioisotope selected from the group consisting of a beta-emitter, a gamma-emitter, and an X-ray emitter. For example, if the radioisotope is a beta-emitter, it may be selected from the group consisting of 90Y, 188Re, 32P, 186Re, 106Rh, and 89Sr; if the radioisotope is a gamma-emitter, it may be selected from the group consisting of 60Co, 137Cs, and 192Ir; or if the radioisotope is an X-ray emitter, it may be selected from the group consisting of 103Pd, 109Cd, 145Sm, 149Pm, 169Yb, and 125I.
In other embodiments of the graduated catheter of the invention, the catheter tube further includes
(a) an inlet orifice positioned along the catheter tube for withdrawing a composition from the bodily lumen and a third lumen extending longitudinally within the catheter tube from the proximal portion and communicating with the inlet orifice,
(b) an outlet orifice positioned along the catheter tube for providing a composition to the bodily lumen and a fourth lumen extending longitudinally within the catheter tube from the proximal portion and communicating with the outlet orifice, or
(c) both.
The graduated catheter of the invention may further comprise a sleeve surrounding at least a portion of the catheter tube. The tubular body of the graduated catheter may have a diameter sufficiently small to fit within a human urethra, and may have a sufficient length that the distal end thereof may be inserted into a ureter of the subject.
The invention also relates to a matched pair of graduated catheters. The matched pair comprises a first and a second graduated catheter of the invention. The position of the indicator of the first catheter along the longitudinal axis of the bodily lumen when the first catheter is seated therein has a known relationship to the position of the indicator of the second catheter along the longitudinal axis of the bodily lumen when the second catheter is seated therein.
In one aspect, the invention relates to a graduated urethral catheter for use within the urethra of a subject. This catheter comprises
(a) a catheter tube having a proximal portion including a proximal end and a distal portion including a distal end, the distal portion having a balloon inflation orifice, the catheter tube including a first lumen extending longitudinally into the catheter tube from the proximal portion and communicating with the balloon inflation orifice;
(b) a balloon affixed to the distal portion, wherein the interior of the balloon communicates with the balloon inflation orifice; and
(c) at least one indicator associated with the catheter tube for indicating a reference position within the urethra.
The invention also relates to a urethral catheter kit. This kit comprises a graduated locator catheter and a graduated delivery catheter, each of which is a graduated catheter of the invention. The graduated locator catheter comprises
(a) a locator catheter tube having a proximal portion including a proximal end and a distal portion, the distal portion including a balloon inflation orifice, the locator catheter tube including a lumen extending longitudinally within the locator catheter tube from the proximal portion and communicating with the balloon inflation orifice;
(b) a balloon affixed to the distal portion, wherein the interior of the balloon communicates with the balloon inflation orifice; and
(c) at least one indicator associated with the locator catheter tube for indicating a locator position within a subject""s urethra when the balloon of the graduated locator catheter is seated against the internal urethral orifice of the subject""s bladder.
The graduated delivery catheter comprises
(i) a delivery catheter tube having a proximal portion including a proximal end and a distal portion including a distal end, the distal portion including a balloon inflation orifice, the delivery catheter tube including a first lumen extending longitudinally within the delivery catheter tube from the proximal portion and communicating with the balloon inflation orifice, the delivery catheter tube also including a second lumen extending longitudinally into the delivery catheter tube from the proximal portion;
(ii) a balloon affixed to the distal portion, wherein the interior of the balloon communicates with the balloon inflation orifice; and
(iii) at least one indicator associated with the delivery catheter tube for indicating a reference position within the urethra of the subject when the balloon of the graduated delivery catheter is seated against the internal urethral orifice of the subject""s bladder;
The locator position has a known relationship to the reference position.
The invention also relates to a method of providing radiation to a tissue located in close proximity to a bodily lumen of a subject. This method comprises
(a) inserting into the bodily lumen a graduated delivery catheter of the invention;
(b) thereafter inflating the balloon;
(c) thereafter seating the balloon against an internal orifice of the bodily lumen; and
(d) positioning a radiation source within the second lumen of the graduated delivery catheter.
Radiation is thereby provided to the tissue located in close proximity to the bodily lumen.
The invention further relates to a method of providing radiation to a tissue located in close proximity to a bodily lumen of a subject. This method comprises
(a) inserting into the bodily lumen a graduated locator catheter of the invention;
(b) thereafter inflating the balloon of the graduated locator catheter;
(c) thereafter seating the balloon of the graduated locator catheter against an internal orifice of the bodily lumen;
(d) thereafter identifying, with respect to the indicator of the graduated locator catheter, a position within the bodily lumen which is in close proximity to the tissue;
(e) inserting into the bodily lumen of the subject a graduated delivery catheter of the invention;
(f) thereafter inflating the balloon of the graduated delivery catheter;
(g) thereafter seating the balloon of the graduated delivery catheter against the internal orifice of the bodily lumen; and
(h) positioning, with respect to at least one the indicator of the graduated delivery catheter, a radiation source within the second lumen of the graduated delivery catheter.
The radiation source is thereby located at the position within the bodily lumen which is in close proximity to the tissue. The bodily lumen may, for example, be the urethra, in which instance the tissue may, for example, be selected from the group consisting of a urethral tissue, a strictured urethral tissue, a urethral tissue at risk for stricture formation, a ureteric tissue, a strictured ureteric tissue, a ureteric tissue at risk for stricture formation, prostate tissue, cancerous prostate tissue, and benign hypertrophic prostate tissue.
The invention still further relates to a method of providing radiation to a tissue located in close proximity to the urethra of a subject. This method comprises
(a) inserting into the urethra a graduated delivery catheter of the invention;
(b) thereafter inflating the balloon within the subject""s bladder;
(c) thereafter seating the balloon against the internal urethral orifice of the bladder; and
(d) positioning a radiation source within the second lumen of the graduated delivery catheter.
Radiation is thereby provided to the tissue located in close proximity to the urethra.
The invention also relates to a method of providing radiation to a tissue located in close proximity to the urethra of a subject. This method comprises
(a) inserting into the urethra a graduated locator catheter of the invention;
(b) thereafter inflating the balloon of the graduated locator catheter in the subject""s bladder;
(c) thereafter seating the balloon of the graduated locator catheter against the internal urethral orifice of the bladder;
(d) thereafter identifying, with respect to an indicator of the graduated locator catheter, a position within the urethra which is in close proximity to the tissue;
(e) inserting into the urethra of the subject a graduated delivery catheter of the invention
(f) thereafter inflating the balloon of the graduated delivery catheter within the subject""s bladder;
(g) thereafter seating the balloon of the graduated delivery catheter against the internal urethral orifice of the bladder; and
(h) positioning, with respect to at least one the indicator of the graduated delivery catheter, a radiation source within the second lumen of the graduated delivery catheter.
Because the indicators on the graduated locator catheter and the graduated delivery catheter have a known positional relationship, the radiation source is located at the position within the urethra which is in close proximity to the tissue.
In another aspect, the invention relates to a graduated ureteric catheter for use within a ureter of a subject. The graduated ureteric catheter comprises a catheter tube and at least one indicator associated with the catheter tube for indicating a reference position within the ureter.
In still another aspect, the invention relates to graduated catheter for indicating a position within a bodily lumen of an animal. This catheter comprises a tubular body having a distal portion for inserting into the bodily lumen and an indicator associated with the distal portion for indicating a position within the bodily lumen.